Papillary renal cell carcinoma with metastatic laparoscopic port site and vaginal involvement: a case report

10.1186/1752-1947-5-131Journal of Medical Case Reports513

Perceived Discrimination and Health Outcomes Among Asian Indians in the United States

Background: Perceived interpersonal discrimination while seeking healthcare services is associated with poor physical and mental health. Yet, there is a paucity of research among Asian Americans or its subgroups. This study examined the correlates of reported interpersonal discrimination when seeking health care among a large sample of Asian Indians, the 3rd largest Asian American subgroup in the US, and identify predictors of adverse self-rated physical health, a well-accepted measure of overall health status. Methods: Cross-sectional survey. Participants comprised of 1824 Asian Indian adults in six states with higher concentration of Asian Indians. Results: Mean age and years lived in the US was 45.7 ± 12.8 and 16.6 ± 11.1 years respectively. The majority of the respondents was male, immigrants, college graduates, and had access to care. Perceived interpersonal discrimination when seeking health care was reported by a relatively small proportion of the population (7.2 %). However, Asian Indians who reported poor self-rated health were approximately twice as likely to perceived discrimination when seeking care as compared to those in good or excellent health status (OR 1.88; 95 % CI 1.12–3. 14). Poor self-rated health was associated with perceived health care discrimination after controlling for all of the respondent characteristics (OR 1.93; 95 % CI: 1.17–3.19). In addition, Asian Indians who lived for more than 10 years in the U.S. (OR 3.28; 95 % CI: 1.73–6.22) and had chronic illnesses (OR 1.39; 95 % CI: 1.17–1.64) (p \u3c 0.05) were more likely to perceive discrimination when seeking health care. However, older Asian Indians, over the age of 55 years, were less likely to perceive discrimination than those aged 18–34 years Indian American. Conclusion: Results offers initial support for the hypothesis that Asian Indians experience interpersonal discrimination when seeking health care services and that these experiences may be related to poor self-rated health status

Anticipatory nausea in cyclical vomiting

BACKGROUND: Cyclical Vomiting Syndrome (CVS) is characterised by discrete, unexplained episodes of intense nausea and vomiting, and mainly affects children and adolescents. Comprehending Cyclical Vomiting Syndrome requires awareness of the severity of nausea experienced by patients. As a subjective symptom, nausea is easily overlooked, yet is the most distressing symptom for patients and causes many behavioural changes during attacks. CASE PRESENTATION: This first-hand account of one patient's experience of Cyclical Vomiting Syndrome shows how severe nausea contributed to the development of anticipatory nausea and vomiting (ANV), a conditioned response frequently observed in chemotherapy patients. This conditioning apparently worsened the course of the patient's disease. Anticipatory nausea and vomiting has not previously been recognised in Cyclical Vomiting Syndrome, however predictors of its occurrence in oncology patients indicate that it could complicate many cases. CONCLUSION: We suggest a model whereby untreated severe and prolonged nausea provokes anxiety about further cyclical vomiting attacks. This anxiety facilitates conditioning, thus increasing the range of triggers in a self-perpetuating manner. Effective management of the nausea-anxiety feedback loop can reduce the likelihood of anticipatory nausea and vomiting developing in other patients

Heregulin β1 drives gefitinib-resistant growth and invasion in tamoxifen-resistant MCF-7 breast cancer cells

Introduction Resistance to anti-epidermal growth factor receptor (anti-EGFR) therapies is an emerging clinical problem. The efficacy of anti-EGFR therapies can be influenced by the presence of heregulins (HRGs), which can bind erbB3/4 receptors and can activate alternative signalling pathways. In the present study we have examined whether HRG signalling can circumvent EGFR blockade in an EGFR-positive tamoxifen-resistant MCF-7 (Tam-R) breast cancer cell line. Methods Tam-R cells, incubated with the selective EGFR tyrosine kinase inhibitor gefitinib ('Iressa', ZD1839), were exposed to HRGβ1 and the effects on erbB receptor dimerization profiles and on activation of associated downstream signalling components were assessed by immunoprecipitation, western blotting and immunocytochemistry. The effects of HRGβ1 on gefitinib-treated Tam-R cell growth and invasion were also examined, and HRGβ1 expression levels were assessed in breast cancer tissue by immunohistochemistry to address the potential clinical relevance of such a resistance mechanism. Results In Tam-R cells, HRGβ1 promoted erbB3/erbB2 and erbB3/EGFR heterodimerization, promoted ERK1/2 and AKT pathway activation and increased cell proliferation and invasion. Gefitinib prevented HRGβ1-driven erbB3/EGFR heterodimerization, ERK1/2 activation and Tam-R cell proliferation, but HRGβ1-driven erbB3/erbB2 heterodimerization, AKT activation and Tam-R cell invasion were maintained. A combination of gefitinib and the phosphatidylinositol 3-kinase inhibitor LY294002 effectively blocked HRGβ1-mediated intracellular signalling activity, growth and invasion in Tam-R cells. Similarly, targeting erbB2 with trastuzumab in combination with gefitinib in Tam-R cells reduced HRGβ1-induced erbB2 and ERK1/2 activity; however, HRGβ1-driven AKT activity and cell growth were maintained while cell invasion was significantly enhanced with this combination. In clinical tissue all samples demonstrated cytoplasmic tumour epithelial HRGβ1 protein staining, with expression correlating with EGFR positivity and activation of both AKT and ERK1/2. Conclusion HRGβ1 can overcome the inhibitory effects of gefitinib on cell growth and invasion in Tam-R cells through promotion of erbB3/erbB2 heterodimerization and activation of the phosphatidylinositol 3-kinase/AKT signalling pathway. This may have implications for the effectiveness of anti-EGFR therapies in breast cancer as HRGβ1 is enriched in many EGFR-positive breast tumours

Molecular mechanism of activation-triggered subunit exchange in Ca(2+)/calmodulin-dependent protein kinase II.

Activation triggers the exchange of subunits in Ca(2+)/calmodulin-dependent protein kinase II (CaMKII), an oligomeric enzyme that is critical for learning, memory, and cardiac function. The mechanism by which subunit exchange occurs remains elusive. We show that the human CaMKII holoenzyme exists in dodecameric and tetradecameric forms, and that the calmodulin (CaM)-binding element of CaMKII can bind to the hub of the holoenzyme and destabilize it to release dimers. The structures of CaMKII from two distantly diverged organisms suggest that the CaM-binding element of activated CaMKII acts as a wedge by docking at intersubunit interfaces in the hub. This converts the hub into a spiral form that can release or gain CaMKII dimers. Our data reveal a three-way competition for the CaM-binding element, whereby phosphorylation biases it towards the hub interface, away from the kinase domain and calmodulin, thus unlocking the ability of activated CaMKII holoenzymes to exchange dimers with unactivated ones

Search for new phenomena in final states with an energetic jet and large missing transverse momentum in pp collisions at √ s = 8 TeV with the ATLAS detector

Results of a search for new phenomena in final states with an energetic jet and large missing transverse momentum are reported. The search uses 20.3 fb−1 of √ s = 8 TeV data collected in 2012 with the ATLAS detector at the LHC. Events are required to have at least one jet with pT > 120 GeV and no leptons. Nine signal regions are considered with increasing missing transverse momentum requirements between Emiss T > 150 GeV and Emiss T > 700 GeV. Good agreement is observed between the number of events in data and Standard Model expectations. The results are translated into exclusion limits on models with either large extra spatial dimensions, pair production of weakly interacting dark matter candidates, or production of very light gravitinos in a gauge-mediated supersymmetric model. In addition, limits on the production of an invisibly decaying Higgs-like boson leading to similar topologies in the final state are presente

Search for the neutral Higgs bosons of the minimal supersymmetric standard model in pp collisions at root s=7 TeV with the ATLAS detector

A search for neutral Higgs bosons of the Minimal Supersymmetric Standard Model (MSSM) is reported. The analysis is based on a sample of proton-proton collisions at a centre-of-mass energy of 7TeV recorded with the ATLAS detector at the Large Hadron Collider. The data were recorded in 2011 and correspond to an integrated luminosity of 4.7 fb-1 to 4.8 fb-1. Higgs boson decays into oppositely-charged muon or τ lepton pairs are considered for final states requiring either the presence or absence of b-jets. No statistically significant excess over the expected background is observed and exclusion limits at the 95% confidence level are derived. The exclusion limits are for the production cross-section of a generic neutral Higgs boson, φ, as a function of the Higgs boson mass and for h/A/H production in the MSSM as a function of the parameters mA and tan β in the mhmax scenario for mA in the range of 90GeV to 500 GeV. Copyright CERN

Continuous-time modeling of cell fate determination in Arabidopsis flowers

<p>Abstract</p> <p>Background</p> <p>The genetic control of floral organ specification is currently being investigated by various approaches, both experimentally and through modeling. Models and simulations have mostly involved boolean or related methods, and so far a quantitative, continuous-time approach has not been explored.</p> <p>Results</p> <p>We propose an ordinary differential equation (ODE) model that describes the gene expression dynamics of a gene regulatory network that controls floral organ formation in the model plant <it>Arabidopsis thaliana</it>. In this model, the dimerization of MADS-box transcription factors is incorporated explicitly. The unknown parameters are estimated from (known) experimental expression data. The model is validated by simulation studies of known mutant plants.</p> <p>Conclusions</p> <p>The proposed model gives realistic predictions with respect to independent mutation data. A simulation study is carried out to predict the effects of a new type of mutation that has so far not been made in <it>Arabidopsis</it>, but that could be used as a severe test of the validity of the model. According to our predictions, the role of dimers is surprisingly important. Moreover, the functional loss of any dimer leads to one or more phenotypic alterations.</p

The spatial scale of density-dependent growth and implications for dispersal from nests in juvenile Atlantic salmon

By dispersing from localized aggregations of recruits, individuals may obtain energetic benefits due to reduced experienced density. However, this will depend on the spatial scale over which individuals compete. Here, we quantify this scale for juvenile Atlantic salmon (Salmo salar) following emergence and dispersal from nests. A single nest was placed in each of ten replicate streams during winter, and information on the individual positions (±1 m) and the body sizes of the resulting young-of-the-year (YOY) juveniles was obtained by sampling during the summer. In six of the ten streams, model comparisons suggested that individual body size was most closely related to the density within a mean distance of 11 m (range 2–26 m). A link between body size and density on such a restricted spatial scale suggests that dispersal from nests confers energetic benefits that can counterbalance any survival costs. For the four remaining streams, which had a high abundance of trout and older salmon cohorts, no single spatial scale could best describe the relation between YOY density and body size. Energetic benefits of dispersal associated with reduced local density therefore appear to depend on the abundance of competing cohorts or species, which have spatial distributions that are less predictable in terms of distance from nests. Thus, given a trade-off between costs and benefits associated with dispersal, and variation in benefits among environments, we predict an evolving and/or phenotypically plastic growth rate threshold which determines when an individual decides to disperse from areas of high local density

Genomics of Signaling Crosstalk of Estrogen Receptor α in Breast Cancer Cells

BACKGROUND: The estrogen receptor alpha (ERalpha) is a ligand-regulated transcription factor. However, a wide variety of other extracellular signals can activate ERalpha in the absence of estrogen. The impact of these alternate modes of activation on gene expression profiles has not been characterized. METHODOLOGY/PRINCIPAL FINDINGS: We show that estrogen, growth factors and cAMP elicit surprisingly distinct ERalpha-dependent transcriptional responses in human MCF7 breast cancer cells. In response to growth factors and cAMP, ERalpha primarily activates and represses genes, respectively. The combined treatments with the anti-estrogen tamoxifen and cAMP or growth factors regulate yet other sets of genes. In many cases, tamoxifen is perverted to an agonist, potentially mimicking what is happening in certain tamoxifen-resistant breast tumors and emphasizing the importance of the cellular signaling environment. Using a computational analysis, we predicted that a Hox protein might be involved in mediating such combinatorial effects, and then confirmed it experimentally. Although both tamoxifen and cAMP block the proliferation of MCF7 cells, their combined application stimulates it, and this can be blocked with a dominant-negative Hox mutant. CONCLUSIONS/SIGNIFICANCE: The activating signal dictates both target gene selection and regulation by ERalpha, and this has consequences on global gene expression patterns that may be relevant to understanding the progression of ERalpha-dependent carcinomas